PTK787/ZK 222584 in Treating Patients With Unresectable Malignant Mesothelioma

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00053885

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: PTK787/ZK 222584 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase II trial to study the effectiveness of PTK787/ZK 222584 in treating patients with unresectable malignant mesothelioma.

Condition or Disease	Intervention/Treatment	Phase
Malignant Mesothelioma	Drug: PTK787/ZK 222584	Phase 2

Detailed Description

OBJECTIVES:

Determine the efficacy of PTK787/ZK 222584, in terms of 3-month progression-free survival, in patients with malignant mesothelioma.
Determine the response rate in patients treated with this drug.
Determine the toxicity of this drug in these patients.
Determine the overall and failure-free survival of patients treated with this drug.
Correlate pretreatment circulating serum levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor, and VEGF mRNA isoforms with response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral PTK787/ZK 222584 daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of PTK787/ZK222584 (NSC#719335) in Patients With Unresectable Malignant Mesothelioma

Study Start Date :

Jul 1, 2003

Actual Primary Completion Date :

Jul 1, 2005

Actual Study Completion Date :

Jun 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PTK787/ZK 222584 Patients receive oral PTK787/ZK 222584 daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.	Drug: PTK787/ZK 222584 oral

Arm

Intervention/Treatment

Experimental: PTK787/ZK 222584

Patients receive oral PTK787/ZK 222584 daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

Drug: PTK787/ZK 222584

oral

Outcome Measures

Primary Outcome Measures

Survival [Up to 3 years post-treatment]
Failure free survival [Up to 3 years post-treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed malignant mesothelioma of 1 of the following types:
Epithelial
Sarcomatoid
Mixed
Not amenable to radiotherapy or curative surgery
Any site of origin including, but not limited to, the following:
Pleura
Peritoneum
Pericardium
Tunica vaginalis
At least one unidimensionally measurable lesion outside of prior irradiation port
At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
The following are not considered measurable:
Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusion
Lymphangitis cutis/pulmonis
Abdominal masses that are not confirmed and followed by imaging techniques
Cystic lesions
No known brain metastases

PATIENT CHARACTERISTICS:

Age

Over 18

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST no greater than 2.5 times ULN

Renal

Creatinine no greater than 1.5 times ULN
Negative for proteinuria by dipstick OR
Urinary protein no greater than 500 mg and creatinine clearance at least 50 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-barrier contraception
No currently active second malignancy except non-melanoma skin cancers (unless therapy is completed and risk of relapse is less than 30%)
No other concurrent uncontrolled illness
No ongoing active infections
No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior signal transduction inhibitor therapy
No prior angiogenesis inhibitor therapy

Chemotherapy

No prior cytotoxic chemotherapy for this malignancy
No concurrent chemotherapeutic agents
Prior intrapleural cytotoxic or sclerosing therapy (including bleomycin) allowed

Endocrine therapy

No concurrent hormonal therapy except steroids for adrenal failure or hormones for non-disease-related conditions (e.g., insulin for diabetes)

Radiotherapy

See Disease Characteristics
At least 4 weeks since prior radiotherapy
No concurrent palliative radiotherapy

Surgery

See Disease Characteristics
At least 2 weeks since prior major surgery

Other

At least 30 days since prior investigational agents
At least 7 days since prior grapefruit or grapefruit juice
At least 7 days since prior CYP3A4 inducers
No prior PTK787/ZK 222584
No prior tyrosine kinase inhibitor therapy
No other concurrent investigational agents
No concurrent isoenzyme inducers or inhibitors of p450
No concurrent warfarin or similar oral anticoagulants
Heparin allowed
No concurrent grapefruit or grapefruit juice
No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northeast Alabama Regional Medical Center	Anniston	Alabama	United States	36207
2	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama	United States	35233-1996
3	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
4	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
5	Naval Medical Center - San Diego	San Diego	California	United States	92134-3202
6	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
7	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
8	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
9	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
10	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
11	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5001
12	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia	United States	20422
13	Broward General Medical Center	Fort Lauderdale	Florida	United States	33316
14	Memorial Regional Cancer Center at Memorial Regional Hospital	Hollywood	Florida	United States	33021
15	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
16	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
17	MBCCOP - University of Illinois at Chicago	Chicago	Illinois	United States	60612
18	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois	United States	60612
19	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
20	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
21	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615-7828
22	West Suburban Center for Cancer Care	River Forest	Illinois	United States	60305
23	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana	United States	46885-5099
24	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
25	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
26	Baptist Hospital East - Louisville	Louisville	Kentucky	United States	40207
27	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
28	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
29	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts	United States	01655
30	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan	United States	49085
31	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
32	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
33	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
34	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
35	CCOP - Kansas City	Kansas City	Missouri	United States	64131
36	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
37	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
38	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
39	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
40	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada	United States	89106
41	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
42	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
43	Cancer Institute of New Jersey at the Cooper University Hospital	Camden	New Jersey	United States	08103
44	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
45	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
46	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	East Syracuse	New York	United States	13057
47	Elmhurst Hospital Center	Elmhurst	New York	United States	11373
48	Queens Cancer Center of Queens Hospital	Jamaica	New York	United States	11432
49	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
50	North Shore University Hospital	Manhasset	New York	United States	11030
51	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
52	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
53	Mount Sinai Medical Center	New York	New York	United States	10029
54	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
55	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
56	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina	United States	28805
57	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
58	NorthEast Oncology Associates - Concord	Concord	North Carolina	United States	28025
59	Veterans Affairs Medical Center - Durham	Durham	North Carolina	United States	27705
60	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
61	Cape Fear Valley Health System	Fayetteville	North Carolina	United States	28302-2000
62	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
63	Lenoir Memorial Cancer Center	Kinston	North Carolina	United States	28503-1678
64	Comprehensive Cancer Center at Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
65	Zimmer Cancer Center at New Hanover Regional Medical Center	Wilmington	North Carolina	United States	28402-9025
66	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
67	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio	United States	43210-1240
68	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
69	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
70	Lifespan: The Miriam Hospital	Providence	Rhode Island	United States	02906
71	University of Tennessee Cancer Institute at Methodist Central Hospital	Memphis	Tennessee	United States	38104
72	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee	United States	38104
73	Veterans Affairs Medical Center - Dallas	Dallas	Texas	United States	75219
74	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390-8852
75	Vermont Cancer Center at University of Vermont	Burlington	Vermont	United States	05401-3498
76	Martha Jefferson Hospital	Charlottesville	Virginia	United States	22902
77	Virginia Oncology Associates - Norfolk	Norfolk	Virginia	United States	23502
78	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037
79	Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke	Roanoke	Virginia	United States	24014
80	St. Mary's Medical Center	Huntington	West Virginia	United States	25701